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Hope Through Research

At MDA, we take a big picture perspective across the full spectrum of neuromuscular diseases to uncover scientific and medical breakthroughs that accelerate treatments and cures. The power in our research approach is that we can often apply learnings from one disease to progress in others to bring urgently-needed answers to our families.

Friedreich's Ataxia (FA)

Friedreich ataxia (FA) is an inherited neuromuscular disease caused by mutations in the gene for frataxin. The mutation leads to a reduction in the level of frataxin protein inside mitochondria — tiny cellular "factories" that use oxygen to produce energy.

Iron is essential for this process, but if too much of it is left floating around freely inside mitochondria, it can trigger oxidative stress. Frataxin appears to act as a storage depot for iron, releasing it only when it’s needed. When frataxin is missing or defective, free iron accumulates in mitochondria, and oxidative stress damages the mitochondria. Frataxin also provides the iron needed for synthesis of several key enzymes in the mitochondria. Therefore, a deficiency of frataxin results in a deficiency of these enzymes, further reducing mitochondrial function.

The frataxin gene normally contains a “trinucleotide repeat,” a section of three DNA nucleotides, G-A-A, that repeat between 5 and 30 times. This section can expand, however. Genes that cause FA have repeats longer than 65 GAA units, and may be more than a thousand units. Genes with repeats between 30 and 65 units are called “premutations,” which do not contribute to disease but are prone to expand in future generations.

Therapeutic Strategies

Because FA is caused by loss of frataxin, therapeutic strategies include increasing production of frataxin from the patient’s own genes, inserting a normal frataxin gene, and administering normal frataxin protein. Other strategies attempt to mitigate the effects of reduced frataxin in mitochondria. These include antioxidant therapies and decreasing iron toxicity.

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